Genetic impact of blood C-reactive protein levels on chronic spinal & widespread pain.
Eur Spine J
; 32(6): 2078-2085, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-37069442
ABSTRACT
PURPOSE:
Causal mechanisms underlying systemic inflammation in spinal & widespread pain remain an intractable experimental challenge. Here we examined whether (i) associations between blood C-reactive protein (CRP) and chronic back, neck/shoulder & widespread pain can be explained by shared underlying genetic variants; and (ii) higher CRP levels causally contribute to these conditions.METHODS:
Using genome-wide association studies (GWAS) of chronic back, neck/shoulder & widespread pain (N = 6063-79,089 cases; N = 239,125 controls) and GWAS summary statistics for blood CRP (Pan-UK Biobank N = 400,094 & PAGE consortium N = 28,520), we employed cross-trait bivariate linkage disequilibrium score regression to determine genetic correlations (rG) between these chronic pain phenotypes and CRP levels (FDR < 5%). Latent causal variable (LCV) and generalised summary data-based Mendelian randomisation (GSMR) analyses examined putative causal associations between chronic pain & CRP (FDR < 5%).RESULTS:
Higher CRP levels were genetically correlated with chronic back, neck/shoulder & widespread pain (rG range 0.26-0.36; P ≤ 8.07E-9; 3/6 trait pairs). Although genetic causal proportions (GCP) did not explain this finding (GCP range - 0.32-0.08; P ≥ 0.02), GSMR demonstrated putative causal effects of higher CRP levels contributing to each pain type (beta range 0.027-0.166; P ≤ 9.82E-03; 3 trait pairs) as well as neck/shoulder pain effects on CRP levels (beta [S.E.] 0.030 [0.021]; P = 6.97E-04).CONCLUSION:
This genetic evidence for higher CRP levels in chronic spinal (back, neck/shoulder) & widespread pain warrants further large-scale multimodal & prospective longitudinal studies to accelerate the identification of novel translational targets and more effective therapeutic strategies.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteína C-Reativa
/
Dor Crônica
Tipo de estudo:
Clinical_trials
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article